[关键词]
[摘要]
近年来,肿瘤免疫治疗迅速发展,其中以T淋巴细胞(T细胞)为主体的过继细胞治疗在临床上取得了一定的疗效,成为最具潜力的免疫治疗方法之一。T细胞归巢主要包括滚动、黏附、外渗和趋化等一系列过程。然而,在实体瘤中存在物理屏障、趋化因子不匹配、血管异常、免疫抑制微环境等因素限制了过继性细胞治疗的疗效。通过改善细胞表面的趋化因子受体、嵌插靶向肽、改进给药方式以及采用联合放疗、免疫检查点阻断剂、肿瘤疫苗、双特异性抗体等治疗方法,可进一步改善T细胞的归巢能力。本文主要对T细胞归巢过程、T细胞靶向肿瘤部位的影响因素以及相关治疗策略做总结与展望。
[Key word]
[Abstract]
In recent years, tumor immunotherapy has developed rapidly, among which T-cell-based adoptive cell therapy has achieved certain clinical effect and become one of the most potential immunotherapeutics. T cell infiltration mainly includes rolling, adhesion, extravasation and chemotaxis etc. However, there are physical barriers, chemokine mismatch, vascular abnormalities, immunosuppressive microenvironment and other factors that limit the efficacy of adoptive cell therapy. The homing ability of T cells can be further improved by optimizing the chemokine receptor on the cell surface, inserting targeted peptide, improving the way of administration, and adopting combined treatment of radiotherapy, immune checkpoint blocker, tumor vaccine and bispecific antibody, etc. This review mainly summarizes the process of T cell infiltration, the influencing factors of T cell targeting tumor site and the relevant treatment strategies, as well as gives a prospection for future research.
[中图分类号]
R730.51;R730.58
[基金项目]
国家自然科学基金资助项目(No. 81872146);江苏省自然科学基金资助项目(No. BK20191114);南京市卫生青年人才培养工程资助项目(No. QRX17038)